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The suppression of macrophage secretion by calcium blockers and adenosine
H Shen1, M D Wiederhold, D W Ou
1Department of Pathology, College of Medicine, University of Illinois at Chicago, USA.
Abstract:
In an effort to examine the effects of calcium blockers and adenosine on superoxide, hydrogen peroxide, and nitrite secretions by mouse peritoneal macrophages, we have utilized the phenol red method, the superoxide dismutase-inhibitable reduction of ferricytochrome c method, and the Griess reagent method to test products after treating periodate-elicited mouse peritoneal macrophages with verapamil, nifedipine, and adenosine. The results show that after treating the macrophages with chemicals 10 minutes before adding PMA (100 ng/ml), all three chemicals inhibited superoxide (O2-) and hydrogen peroxide (H2O2) secretions dose-dependently, yet they failed to suppress macrophage reactive oxygen intermediates (ROI) after a 24 hour treatment. On the other hand, calcium blockers, verapamil and nifedipine, could reduce nitrite secretion (NO2-), while adenosine did not show the ability to inhibit NO2-. This indicates that calcium, as a secondary messenger, is important for the production of ROI and RNI. The reason behind the loss of the ability to suppress macrophage ROI production in a 24 hour treatment remains unexplored.
Insights
Calcium blockers and adenosine inhibit macrophage secretions of superoxide and hydrogen peroxide. Verapamil and nifedipine reduce nitrite, but adenosine does not, highlighting calcium's role in reactive oxygen and nitrogen intermediates.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Macrophages play a crucial role in immune responses through the secretion of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI).
- Calcium ions act as secondary messengers in cellular signaling pathways, influencing various cellular functions, including immune cell activation and mediator release.
- Understanding the modulatory effects of pharmacological agents on macrophage function is essential for developing targeted immunotherapies.
Purpose of the Study:
- To investigate the impact of calcium channel blockers (verapamil, nifedipine) and adenosine on the secretion of superoxide (O2-), hydrogen peroxide (H2O2), and nitrite (NO2-) by mouse peritoneal macrophages.
- To elucidate the role of calcium as a secondary messenger in the production of ROI and RNI in macrophages.
Main Methods:
- Periodate-elicited mouse peritoneal macrophages were treated with verapamil, nifedipine, and adenosine.
- Superoxide and hydrogen peroxide secretions were measured using the phenol red and superoxide dismutase-inhibitable reduction of ferricytochrome c methods, respectively.
- Nitrite secretion was quantified using the Griess reagent method.
Main Results:
- Verapamil, nifedipine, and adenosine inhibited superoxide and hydrogen peroxide secretions in a dose-dependent manner when added 10 minutes before phorbol 12-myristate 13-acetate (PMA) stimulation.
- Calcium blockers (verapamil, nifedipine) significantly reduced nitrite secretion, whereas adenosine did not.
- The inhibitory effect on ROI was lost after a 24-hour treatment with the tested chemicals.
Conclusions:
- Calcium channel blockers and adenosine can modulate macrophage inflammatory mediator production, particularly in the short term.
- Calcium is implicated as a critical secondary messenger in the production of both ROI and RNI by macrophages.
- The mechanisms underlying the loss of inhibitory effects on ROI after prolonged exposure require further investigation.